Finding a method capable separating the effects of neuroleptics on
motivational control from those on motoric control has been difficult.
Aparicio (1998) proposed the barrier choice paradigm to assess the
effects of neuroleptics on motivational and motoric elements of operant
responding within the same experimental situation. In this methodd food
became available to rats by pressing two concurrently available levers.
A barrier of 15 cm between the levers obstructed direct passage from one
lever to the other, obligating the rats to climb the barrier when
traveling from one lever to the other. By raising the barrier from 15 to
76 cm, Aparicio increased the travel distance between the lever while
assessing four doses of haloperidol (0.02, 0.04, 0.08, and 0.16 mg/kg)
across each barrier size. He found that raising the barrier or
increasing the dose of haloperidol had similar effects on choice, the
rats stayed longer on one side of the chamber and made more presses on
that lever producing food reinforcers. That is, haloperidol impeded
climbing the barrier at doses that did not impair food maintained lever
pressing (Aparicio, 1998). In additional choice studies, where the rate
of food deliveries varied across two (Aparicio, 1999, 2003a) or eight
(Aparicio & Velasco, 2003) alternatives, haloperidol decreased the
overall response output without affecting response allocation
(interestingly, the highest doses of haloperidol produced exclusive
preference for one alternative, but not necessarily the richer
alternative). Similarly, haloperidol did not interfere with adaptation
to rapid changes in contingencies of reinforcement (Aparicio, 2003b),
nor did it affect choice controlled by different rates and amounts of
reinforcers (Aparicio, 2007a). These results are not consistent with the
notion that this drug causes anhedonic effects (Aparicio, 2007b).

Because of the cumulative body of evidence inconsistent with the
anhedonia hypothesis, some researchers in neuroscience have focused on
aspects of behavior such as vigor or persistence of work output in
foraging activities, claiming: 1) that animals continually make choices
based upon cost/benefit analyses, and 2) dopamine in nucleus accumbens
is involved in behavioral activation, exertion of effort, and
effort-related choices, Salamond & Correa, 2002; Salamone et al.,
1991, 1997). These ideas come from studies (Salamone, Cousing &
Bucher, 1994; Cousins, Atherton, Turner & Salamone, 1996) showing
that neuroleptics make animals less likely to respond to alternatives
requiring a high cost (e.g., climb a wall and press a lever) to produce
a preferred food (i.e., foodpellets), shifting preference towards an
alternative requiring a low cost (e.g., sitting in the chamber) where a
non-preferred food (chow) is freely available; that is, the same drugs
(e.g., haloperidol, SKF 83566, or raclopride) that decrease lever
pressing for high-hedonic-value reinforcers (food-pellets) increase the
consumption of chow, the low-hedonic-value food, Cousins et al., 1996;
Cousins, Wel & Salamone, 1997; Cousion et al., 1996; Koch, Schmid,
Schnitzler, 2000).

Other attempts to assess the hedonic value of food reinforcers
within the same situation; Weatherly, Davis & Melville, 2000;
Weatherly & Moulton, 2001; Weatherly, Rue, Davis & Melville
2000; Weatherly, Stout, McMurry, Rue & Melville, 1999) used multiple
schedules of reinforcement with two variable interval (VI) components in
sessions lasting 1 hour, in the first 30 minutes, one VI provided
liquid-sucrose and in the second 30 minutes, the other VI delivered
food-pellets. In these studies of lever pressing maintained by 1 or 5 %
of sucrose solution increased in the first VI if food-pellets, rather
than the same sucrose solution, were delivered in the second VI. The
interpretation of this result is that food-pellets delivered in the
second half of the session represented an increase in the reinforcer
value relative to either 1 or 5 % liquid-sucrose obtained in the first
half of the session (Weatherly; Stout, Davis & Melville, 2001;
Weatherly, Stout, Rue & Melville, 2000, Weatherly, Moulton &
Ritt, 2002; Weatherly, Arthur & Tischar, 2003).

The procedure described in the above studies can be used to assess
the anhedonia hypothesis' claim that neuroleptics diminish the
reinforcing value of food reinforcers. Accordingly, in a multiple
schedule with two VI components, one VI component delivering reinforcers
of relatively low hedonic value (a drop of 5 % liquid--sucrose solution)
and the other VI component delivering reinforcers of relatively high
hedonic value (food-pellets), it would be expected that behavior
maintained by the weaker reinforcer (i.e., sucrosewater) would be more
sensitive to the suppressive effects of haloperidol.

Alternatively, if haloperidol does not reduce reinforcing value of
food reinforcers, but it acts on the motor system by interfering with
the emission of operant responses, then dose-related decreases in lever
presses will occur in both VI components; so, we should expect that the
behavior maintained by both potent (food-pellets) and weak
(sucrosewater) reinforcers will show comparable decreases across doses
of haloperidol.

In four phases using multiple schedules with two VI components, we
explored the above possibilities as follows. Phase 1 determined whether
the hedonic value of food-pellets was higher than that of sucrose -water
reinforcers, changes in lever presses were analyzed in conditions where
the rate of one reinforcer type increased in one VI component, while the
rate of the other reinforcer type remained invariant in the other VI
component. Phase 2 assessed the effects of intra-peritoneal
administrations of haloperidol (0.05, 0.10, 0.15, and 0.20 mg/kg on
reductions in the number of lever presses maintained by the high- and
low-hedonic-value reinforcers (i.e., food pellets, and sucrose water,
respectively). Phase 3 studied the possibility that the white noise
associated with the first VI component and the white light associated
with the second VI component, differed from one another in controlling
different numbers of lever presses in the first and second half of the
session. Thus, phase 3 reversed the order of these stimuli, the light
was associated with the first VI component and the white noise was
associated with the second VI component. Phase 4 assessed the
possibility that subcutaneous administration of haloperidol (0.0125,
0.0250, 0.0500, and 0.0100 mg/kg) is more potent in decreasing lever
pressing than intra-peritoneal administration of haloperidol, because
subcutaneous administration is known to produce longer lasting and
steadier effects on behavior than those produced by intra-peritoneal
administration of haloperidol.

Method

Subjects

Eight male experimentally naive Wistar rats (Harlan Sprague;
Dawley, IN) numbered R50 to R57, were maintained at 85 % of their free
body weights. The rats were approximately 90 days old when the
experiment began and were housed individually with free access to water
in a temperature-controlled colony room on a 12 -light: 12 dark cycle.

Apparatus

Four modular chambers (Coulbourn E10-18TC) for rats measuring 310
mm long, 260 mm wide, and 320 mm high (inside) were enclosed in
sound-attenuating boxes that from the outside measured 780 mm wide, 540
mm long, and 520 mm high. A square metal grid constituted the floor of
each chamber. A lever (E21-03), 30 mm wide and 15 mm long requiring a
force of 0.2 N to operate, was centered on the front wall of each
chamber 100 mm above the floor. A white 24 V DC light bulb (E11-03) was
installed 20 mm above the lever. A food cup (E14-01), 30 mm wide and 40
mm long, was installed 10 mm from the left wall and 20 mm above the
floor. A food dispenser (E14-24) located behind the front wall delivered
45-mg food pellets (Formula A/1 Research Diets) into the food cup. A
water dipper cup containing a 0.05 cc drop of sucrose-water (5 % w/v)
was installed 10 mm from the right wall and 20 mm above the floor. A
speaker (E12-01) 26 mm wide by 40 mm high, was mounted on the front wall
of each chamber 10 mm from the right wall and 20 mm from the ceiling and
connected to a white noise generator (E12-08) which provided a constant
white noise 20 kHz (+/- 3 dB). A white 24 V DC light bulb (E11-03),
which was centered and installed on the ceiling of each chamber,
provided the illumination of the chamber. All experimental events were
arranged on a HP[R] PC- compatible computer running CoulbournPC[R]
software, located in a room remote from the experimental chamber. The
computer recorded the time (10-ms resolution) at which every event
occurred in experimental sessions.

Procedure

Training

The rats were randomly assigned to two groups (Group F-W and Group
W-F) of four each. Rats in Groups F-W and W-F were numbered 50 to 53 and
rats 54 to 57, respectively. In sessions that lasted 30 minutes, each
rat was placed in the chamber with the lever associated with a
continuous schedule of reinforcement. For Group F-W, in these sessions,
each lever press produced a single food pellet; whereas, for Group W-F
in these sessions, each lever press produced 3-s access to 5% liquid
sucrose-water. The session lasted until the rats obtained 60 reinforcer
deliveries. Once the rats were reliably pressing the lever, the
conditions were reversed; for Group F-W and W-F, presses produced liquid
sucrose -water and food-pellets, respectively. Once all rats
consistently pressed the lever, the experiment began.

Phase 1

Phase 1 implemented a multiple schedule of reinforcement with two
variable-interval VI components (i.e., Mult VI VI); each VI component
was presented once per session. For Group F-W the session started by
turning on the house light and the white noise, which signaled the
beginning of the first VI component in which food pellets were delivered
contingent upon lever pressing. After 30 minutes, the white noise and
the house light were turned off, initiating a 1-minute blackout. After
the blackout, the house light and the light above the lever were turned
on, signaling the beginning of the second VI component. For the next 30
minutes, pressing the lever produced sucrosewater reinforcers. In
conditions 1 to 4, the rate of sucrose water deliveries increased (i.e.,
VI value decreased) in the second VI component while the rate of
food-pellets was held constant in the first VI component (see Table 1).

Group W-F was exposed to the same Mult VI VI with the white noise
associated with the first VI component and the light above the lever to
the second VI component, except that the first VI component delivered
sucrose-water and the second VI component delivered food-pellets
contingent upon lever-pressing. In conditions 1 to 4, the rate of
food-pellets increased in the second VI component while the rate of
sucrose-water deliveries was held constant in the first VI component
(see Table 1). Conditions 5 to 8 reversed this manipulation, for Group
W-F the rate of sucrose-water deliveries increased in the first VI
component while the rate of food-pellets remained constant in the second
VI component; whereas for Group F-W the rate of food pellets increased
in the first VI component while the rate of sucrose-water deliveries
remained constant in the second VI component. Table 1 shows VI values
for both VI components across conditions and the number of sessions per
conditions.

Phase 2

Phase 2 used a Mult VI 56 s VI 56 s schedule of reinforcement to
deliver food-pellet and sucrosewater reinforcers at the same rate both
in the first and the second half of the session. In condition 9, the
baseline number of lever presses maintained by food-pellet and
sucrose-water reinforcers was recovered for both groups (F-W and W-F) in
sessions that implemented the same general procedure used in Phase 1.
Then, in conditions 10 to 13 four doses of haloperidol (0.0500, 0.1000,
0.1500, and 0.2000 mg/kg selected from previous studies (Balderrama
& Aparicio, 2008), were administered intraperitoneal (IP) prior to
selected experimental sessions. The drug regimen was conducted in 12-day
blocks and all doses were administered 45 min before the beginning of
drug sessions. On days 1, 4, 7, and 10 (normal days) no injections were
given. On days 2, 5, 8, and 11 (vehicle days) the rats received
injections of a solution of saline water and tartaric acid 45 min before
the beginning of the session. On days 3, 6, 9, and 12 (drug days) only
one dose was injected before the beginning of the session (i.e., a
different dose for each rat was assessed according to a Latin square
design). Injection volume was always 1.0 ml/kg. Control saline/tartaric
acid injections were given to rule out any possible confounding effects
of the injection procedure on the rats' behavior. Haloperidol
(purchased from Sigma Chemical Co. laboratories, St. Louis, MO) was
dissolved in a 0.3% solution of tartaric that which also served as
vehicle solution on control days.

Phase 3

Phase 3 explored the possibility that the white noise associated
with the first VI component and the light above the lever associated
with the second VI component, differed from one another in controlling
lever pressing in the first and the second half of the session,
respectively. In conditions 14 to 17 these stimuli were reversed, the
light above the lever was associated with the first VI component and the
white noise was associated with the second VI component. For Group F-W
the rate of sucrosewater deliveries increased in the second VI component
while the rate of food-pellet deliveries was held constant in the first
VI component; whereas for Group W-F the rate of food-pellet deliveries
increased in the second VI component while the rate of sucrose-water
deliveries was held constant in the first VI component (see Table 1).

Phase 4

In Phase 4, the Mult VI 56 s VI 56 s was reinstituted. For group
F-W, food-pellets and sucrose-water reinforcers were delivered at the
same rate in the first and second half of the session,; whereas for
group W-F, sucrose -water and food-pellets were de - livered at the same
rate in the first and the second half of the session. Then, condition 19
assessed the possibility that subcutaneously administered haloperidol is
more efficient in decreasing lever pressing than it is via IIP Four
doses of haloperidol (0.0125, 0.0250, 0.0500, and 0.1000 mg/kg) were
subcutaneously (SC) administered to the rats 30 minutes before the
beginning of the drug sessions (that time in our experience is enough
for haloperidol to act upon the organism and maintain its maximum
effectiveness for 90 minutes or more.

Data analysis

All sessions were used for the analysis. The daily records of the
total number of presses and the obtained food-pellets or sucrose -water
deliveries were summed up individually for each VI component. These sums
were used to compute average data across sessions. For each 12-day
block, a complete dose effect curve was generated for each rat,
consisting of the average data from the 4 normal days and the 4 vehicle
days, and the data from 1 day at each dose. Conditions 10 to 13
consisted of 4 dose-effect determinations, and condition 19 consisted of
a single dose-effect determination.

Results

Responding under IP pre-drug conditions, Phase 1

The number of lever presses and obtained reinforcers per VI
component under the pre-drug conditions (Phase 1) are summarized in
Table 2. In conditions 1 to 4 the reinforcer rate was manipulated in the
second VI component, and in conditions 5 to 8 reinforcer rate was
manipulated the first VI component. With equal reinforcer rates in both
components (Mult VI 56 s, VI 56 s), the number of lever presses was
substantially higher in the VI component delivering food-pellets,
regardless of whether that VI component was the first or the second VI
component. For group F-W, the average number of presses (and obtained
reinforcers) maintained by food pellets was 453.07 (27.69) and 1212.88
(24.15), respectively in conditions 1 and 5; for group W-F, the
corresponding values were 407.24 (26.43) and 1276.19 (23.73),
respectively. The same conditions show that for group F-W the average
number of presses (and obtained reinforcers) maintained by sucrose water
was 97.58 (19.19) and 227.19 (17.03), and for group W-F they were 87.31
(17.05) and 143.48 (17.60), respectively. Generally, the number of lever
presses per VI component was higher in condition 5 than in condition 1,
suggesting an effect of the rats' experience with both types of
reinforcers. On average (conditions 1 and 5), however, with an equal
reinforcer rate in both components, food-pellet presentation maintained
approximately a number 6-fold times higher of lever presses than did
sucrose-water presentation.

For both groups, increasing the rate of sucrosewater presentation
(conditions 2 to 4 for group F-W and 6 to 8 for group W-F) resulted in
an increase in the average number of presses in that VI component; this
was accompanied by an increase in the average number of presses in the
VI component delivering food pellets, even though the rate of
food-pellet presentation was unchanged, and regardless of whether the
manipulation in the rate of sucrose-water was made in the first or the
second half of the session. For both groups, the average number of
presses increased by increasing the rate of food-pellet presentation
(conditions 6 and 7 for group F-W and conditions 2 and 3 for group W-F),
except at the highest rate (conditions 8 and 4, respectively) at which
the average number of presses declined. For Group W-F, the average
number of presses maintained by sucrose-water increased in the first VI
component with increasing rate of food-pellets in the second VI
component (conditions 2 to 4), even though the rate of sucrose-water
presentation was held constant in the first VI component. In contrast,
for Group F-W the average number of presses maintained by sucrose-water
presentation decreased in the second VI component with increasing rate
of food-pellets in the first VI component (see Table 2).

Effects of IP haloperidol, Phase 2

For both groups, the data of condition 9 (the return to VI 56 s, VI
56 s) were similar (not shown in Table 2) to those obtained in condition
5. For group F-W average number of presses (and obtained reinforcers)
maintained by food-pellet presentation and sucrose-water presentation
was 1576.25 (24.5) and 176.75 (23.7), respectively,; whereas for group
W-F, the average number of presses (and obtained reinforcers) maintained
by sucrose-water presentation and food-pellet presentation was 767.25
(23.0) and 1636.5 (29.2), respectively. Once again, the number of lever
presses was substantially higher in the VI component delivering food
pellets.

Haloperidol dose-effect functions on lever pressing (conditions 10
to 13) for Groups F-W and W-F are shown in Figures 1 and 2,
respectively. The corresponding functions for the reinforcers obtained
are shown in Figures 3 and 4. In each figure, columns 1-4 show data from
successive dose-effect determinations (conditions 10 to 13) via IP
injection. Several features are evident in these functions Uunder
no-drug and vehicle conditions (unconnected symbols), the number of
lever presses maintained by pellet presentation was uniformly higher
than the number of lever presses maintained by sucrose-water
presentation (replicating the data from conditions 1, 5, and 9).
Generally, haloperidol produced dose -related de - creases in lever
pressing and obtained reinforcers in both components. For most of the
rats, the first dose-effect determination yielded roughly parallel
functions in both components. Although there were a few exceptions
(e.g., R53), these decreases in lever pressing (figures 1 and 2) were
not accompanied by substantial reductions in the rate of reinforcer
delivery in either VI component. That is, most of the rats continued to
receive reinforcers in both components figures 3 and 4).

Visual inspection from left to right of columns 1-4 reveals that
the effects of haloperidol on lever pressing increased across successive
dose-effect determinations. That is, sensitization to the
response-suppressing effects of haloperidol developed. This was
typically accompanied by a decline in the rate of reinforcer
presentation. Interestingly, for most of the rats, sensitization
appeared to develop more quickly (R50, R51, R52, R53, R54, R57), and to
a greater extent (R52, R53, R54, R57), in the VI component delivering
sucrose-water than in the VI component delivering food-pellets. Thus,
over the last two or three determinations of the dose -effect function,
pressing the lever maintained sucrose-water presentations was more
likely to be suppressed at a given dose of haloperidol.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

Responding under SC pre-drug conditions, Phase 3

Table 3 summarizes the data for lever presses and obtained
reinforcers for conditions (14 to 17) where the light above the lever
was associated with the first VI component, and the white noise was
associated with the second VI component. The rate of the reinforcers was
manipulated in the second VI component, providing sucrose-water for
group F-W and food-pellets for group W-F. With equal rate of reinforcers
in both components (condition 14), the number of lever presses was
higher in the VI component delivering food pellets than in the component
delivering sucrose water, regardless of whether that VI component was
programmed in the first or the second half of the session. Table 3 shows
for group F-W, the average number of lever presses (and obtained
reinforcers) maintained by food-pellet presentation and sucrose-water
presentation was 98.58 (21.17) and 64.98 (15.33), respectively; whereas
for group W-F, these values were 138.64 (25.28) and 82.81 (19.44),
respectively. For Group F-W, the average number of presses maintained by
food-pellets increased in the first VI component with increasing rate of
sucrose-water in the second VI component (conditions 15 to 17), even
though the rate of food-pellet presentation was held constant in the
first VI component. In contrast, for group W-F the average number of
presses maintained by sucrose-water decreased in the first VI component
with increasing rate of food-pellets in the second VI component (but see
rat 56). Increasing the rate of sucrose-water presentation in the second
VI component (i.e. group F-W) produced a concomitant increase in of
lever pressing in that component. However, group W-F shows unsystematic
changes in lever pressing with increasing rate of food-pellet
presentation in the second VI component.

Effects of SC haloperidol, Phase 4

For group W-F, the data in condition 18 (the return to VI 56 s, VI
56 s) were consistent with those obtained in condition 9, the average
values of presses (and average obtained reinforcers) maintained by
sucrose-water and food-pellets were 137 (18) and 345 (27), respectively
(data not shown in Table 3). However, for group F-W, the average number
of lever presses (and obtained reinforcers) maintained by food-pellet
presentation was lower than the ave - rage number presses maintained by
sucrose-water presentation: 178 (28) versus 229 (20).

Column 5 of Figures 1- 4 shows dose-effect functions on lever
pressing and obtained reinforcers for a single determination of
haloperidol via SC administration (condition 19). Haloperidol produced
dose-related decreases in lever pressing and obtained reinforcers in
both VI components. However, there are two notable differences in these
data compared to those obtained during the IP Phase 2. First, the number
of lever presses per component was similar for the two types of
reinforcers. Second, haloperidol was more potent in decreasing responses
to the lever via SC administration than via IP administration (note the
lower dose range for SC administration). For R53, R54, and R55,
responding maintained by sugar water was more sensitive to SC
administration of haloperidol; whereas, for R50 and R52, responding
maintained by food pellets was more sensitive to SC administration of
haloperidol. For R51 and R56 responding in both VI components was about
equally sensitive tc.SC administration of haloperidol.

In the present study, we used multiple schedules of reinforcement
with two VI components, one VI component delivered food-pellets and the
other VI component delivered sucrose-water reinforcers. With equal rate
of reinforcers in both components (Mult VI 56 s, VI 56 s), we found a
substantially higher number of lever presses in the VI component
delivering food-pellets than in the VI component delivering sucrose
water; this occurred regardless of whether that VI component was
programmed in the first half of the session (group F-W) or in the second
half of the session (group W-F). Pressing the lever, however, was higher
in the redetermination than in the original determination, suggesting
that performance was enhanced with the rats' experience with both
types of reinforcers. These findings are in keeping with the notion that
the reinforcing (i.e., hedonic) value of a 45 mg food pellet is higher
than that of a 0.05 cc drop of 5% sucrose water (e.g., Weatherly &
Moulton, 2001; Weatherly et al., 1999).

Generally, lever pressing increased with increasing the reinforcer
rate, this result occurred regardless of whether the manipulation in the
rate of reinforcers was made in the first or in the second VI component.
At the highest rate of food-pellet reinforcers (VI 7 s), however, the
number of lever presses decreased in that component, probably due to
satiation, given the large quantity (about 200) of food-pellets obtained
in that VI component.

For Group W-F, increasing the rate of foodpellet presentation in
the second VI component produced a concomitant increase in lever
pressing maintained by sucrose-water presentation, even though the rate
of sucrose -water presentation was held constant in the first VI
component. These data resembled those documented in several studies
(e.g., Weatherly et al., 1999; Weatherly, Davis et al., 2000; Weatherly
& Moulton, 2001; Weatherly, Rue et al., 2000), and may qualify as
induction because receiving food pellets in the second VI schedule,
rather than sucrose water, might represent an improvement in the
upcoming conditions of reinforcement (Weatherly et al., 2001, 2002).
Interestingly, however, we found the same result for Group F-W; lever
pressing maintained by food pellets increased in the first VI component
by increasing the rate of sucrose-water presentation in the second VI
component. This result may also qualify as induction, given that the
number of lever presses increased in both VI components. Thus,
regardless of the relative hedonic value of reinforcers presented in the
first or the second VI component, increasing the reinforcer rate in the
second VI component produced an increase in responding in the first
(unchanged) VI component.

Another finding was that the number of lever presses maintained by
sucrose-water presentation decreased in the second (unchanged) VI
component as a function of increasing the rate of food-pellet
presentation in the first VI component (Group F-W). This result can be
considered an example of behavioral contrast, in which the response rate
in an unchanged component of a multiple schedule decreases as a function
of an increase in the reinforcer rate in another component (Bouzas &
Baum, 1976). Interestingly, the number of lever presses maintained by
food-pellet presentation actually increased in the second (unchanged) VI
component as a function of increasing the rate of sucrose-water
presentation in the first VI component (Group W-F), for which we have no
explanation.

Assessing IP administration of haloperidol, Phase 2

Consistent with the results of Phase 1, the redetermination of the
Mult VI 56 s VI 56 s schedule during the no-drug and vehicle conditions
of Phase 2 showed that the number of lever presses maintained by
food-pellet presentation was uniformly higher than the number of lever
presses maintained by sucrose -water presentation, confirming our
conclusion that the reinforcing value of a 45 mg food pellet was greater
than that of 0.05 cc of a 5% sucrose solution.

In both components, the IP administration of haloperidol produced
dose-related decreases in the number of lever presses. In several cases,
these decreases were not accompanied by substantial reductions in the
rate of reinforcer delivery in either VI component. Even at the highest
dose of haloperidol (0.20 mg/kg), several of the rats continued to
produce reinforcers in both VI components. These results are consistent
with the view that decreases in food-maintained operant responding and
decreases in feeding produced by neuroleptics are not necessarily the
result of decreased reinforcing strength (Salamone et al, 1997) or
decreased appetite (Salamone et al, 2002).

The suppressive effects of haloperidol on lever pressing increased
across successive dose-effect determinations; that is, the sensitization
to the response-suppressive effects of haloperidol developed in both
components. Inspection of the data in Figures 1 and 2 indicates that
sensitization appeared to develop more rapidly (i.e., after fewer
administrations), and to a greater extent, in the VI component
delivering sucrose-water than in the component delivering food pellets,
suggesting rate-suppressive effects of haloperidol that depended on the
type of reinforcer. To further assess the possibility that the type of
reinforcer altered the resistance of pressing the lever under the
suppressive effects of haloperidol, we used a statistic proposed by
Nevin, Smith and Roberts(1987) to represent the overall effects of the
behaviorally disruptive event (in this case, the administration of
haloperidol) on lever pressing maintained by food-pellets and
sucrose-water reinforcers. We used the following equation in order to
compute the proportion of baseline responding:

[bar.P] = [SIGMA][x.sub.i][p.sub.i]/[SIGMA][x.sub.i]

Where [x.sub.i] is the ith drug dose and pi the proportion of
baseline responding produced by that dose. Thus, Equation 1 quantifies
the overall effects of a range of values (doses) of a
"disruptive" variable (haloperidol in this case) on
responding. Note that, because the suppressive effects of haloperidol
are dose-related, Equation 1 gives greatet importance to higher doses.
Accordingly, [bar.p] is a weighted mean of the proportional reductions
in lever pressing produced by haloperidol.

The overall means are displayed to the far right of Figure 5, it
shows the [bar.p] value as a function of the successive i.p. dose-effect
curve determination) for Group F-W (top graph) and Group W-F (bottom
graph). Two results are evident: 1) [bar.p] is higher for Group W-F
(range from 0.25 to 0.55) than for Group F-W (range from 0.10 to 0.22),
indicating that pressing the lever was more resistant to the suppressive
effects of haloperidol in Group W-F than in Group F-W; and 2) [bar.p] is
higher for sucrose-water than for food-pellets reinforcers, indicating
that lever pressing maintained by 0.05 cc of 5% sucrose-water
presentation was more resistant to the suppressive effects of
haloperidol than was the lever pressing maintained by 45 mg food-pellet
presentation.

Interestingly, the cumulative proportional rate-suppressive effects
of haloperidol, summarized using the [bar.p] statistic, were greater for
group F-W than for Group W-F, also, the cumulative proportional
rate-suppressive effects of haloperidol were greater for lever presses
maintained by food-pellet reinforcers than for lever presses maintained
by sucrose-water reinforcers. These findings are difficult to conciliate
with the anhedonia hypothesis which might predict: 1) a similar [bar.p]
value for groups F-W and W-F, because the suppressive lever-pressing
effect of haloperidor should be the same regardless of the order in
which the food-pellets and sucrose-water reinforcers were produced in
the session, and 2) a higher [bar.p] value for food-pellets than for
sucrosewater reinforcers, because pressing the lever maintained by
reinforcers of high hedonic value (foodpellets) should be more resistant
to suppression by haloperidol than pressing the lever maintained by
reinforcers of low hedonic value (sucrose-water).

Reversing the stimulus associated with the first and the second VI
component, Phase 3

Phase 3 explored the possibility that in phases 1 and 2 the white
noise and the light above the lever may differed from one another in
controlling lever presses in the first and the second half of the
session, respectively. Thus, it reversed the order in which these
stimuli were presented in the session; the light above the lever was
associated with the first VI component, and the white noise was
associated with the second VI component.

With the rats responding to the Mult VI 56 s VI 56 s, again
pressing the lever was highest in the VI component providing food
pellets; this occurred regardless of whether that VI component was the
first or the second VI component programmed in the session. This result
is consistent with findings of conditions 1, 5, and 9 (and with those of
normal and vehicle days in conditions 10-13 of phase 2) and further
support the notion that the hedonic value of food-pellet reinforcers is
higher than that of sucrose-water reinforcers, Weatherly & Moulton,
2001; Weatherly et al., 1999).

The possibility that the white noise and the light above the lever
had different effectiveness in controlling lever presses, was discarded
by the results of conditions 15 to 17; increasing the rate of
reinforcers in the second VI component produced results in the first VI
component that were consistent with findings corresponding to conditions
2 to 4 and 6 to 8. For Group F-W pressing the lever maintained by
food-pellet reinforcers increased in the first VI component by
increasing rate of sucrose-water reinforcers in the second VI component,
whereas for Group W-F pressing the lever maintained by sucrose-water
presentations decreased with increasing rate of food-pellets in the
second VI component. The unsystematic changes in the average number of
lever presset displayed by Group W-F in the second VI component, and the
fact that the overall performance of both groups was considerably lower
in Phase 3 (less responding occurred in both VI components) than the
overall performance in phases 1 and 2, strongly suggest that the
administration of haloperidol in conditions 10 to 13 of Phase 2 produced
cumulative effects that were carried over to Phase 3. Thus, a reasonable
interpretation of these data is that haloperidol acted upon the motor
system to slow down the lever-pressing behavior (Aparicio, 2003a, 2007b;
Cheeta et al., 1995; Fiberger et al., 1976; Nowen, Arrizi, Carlson &
Salamone, 2001; Pitts & Horvitz, 2000; Salamone, 1992; Tombaugh et
al., 1979).

[FIGURE 5 OMITTED]

Effects of SC haloperidol, Phase 4

In the last redetermination (condition 18) to the Mult VI 56 s VI
56 s, only one the W-F group of rats showed results consistent with
previous redeterminations and the original determination to the Mult VI
56 s VI 56 s; that is, food-pellet presentations maintained more lever
presses (Mean of345) than did sucrose-water presentations (Mean of 137).
For Group F-W, pressing the lever maintained by food-pellets was
slightly lower (Mean of 178 presses) than responding maintained by
sucrose -water reinforcers (Mean of229 presses). This result cannot be
interpreted as a reduction in the hedonic value of food-pellets due to
the rats' experience with haloperidol in Phase 2, because Group F-W
produced and consumed more food-pellet (Mean of 28) than sucrose-water
reinforcers (Mean of 20) in condition 18; moreover, for both groups of
rats, F-W and W-F, the number of food-pellets and sucrose -water
reinforcers obtained in condition 18 was similar to that obtained in the
previous phases. Thus, a more viable explanation for the results of
condition 18 is that the administration of haloperidol in Phase 2
produced cumulative suppressive effects on pressing the lever which
resulted in a reduction of the overall performance of the rats, and
these effects were carried over to phases 3 and 4.

Consistent with the results of Phase 2, haloperidol produced
dose-related decreases in lever pressing and obtained reinforcers in
both VI components. Although haloperidol was more potent in decreasing
lever pressing through s.c. administration than through i.p.
administration, the dose-effect functions for both reinforcers were
similar during s.c. administration, suggesting that lever pressing
maintained by food-pellets and lever pressing maintained by
sucrose-water reinforcers were equally resistant to the disruptive
effects of haloperidol. To further assess this possibility, we again
used Nevin et al. (1987) statistic to represent the overall effects of
the behavioral disruptive variable, haloperidol, on lever pressing
maintained by food-pellets and sucrose-water reinforcers.

Figure 6 shows the [bar.p] value computed for lever presses
maintained by food-pellets and sucrosewater reinforcers. For Group F-W
(top graph) [bar.p] was again higher for sucrose-water than for
foodpellet reinforcers, indicating that the pressing of the lever
maintained by sucrose-water reinforcers was more resistant to the
suppressive effects of haloperidol than the pressing of the lever
maintained by food-pellet reinforcers. Group W-F (bottom graph) shows
similar values for [bar.p] for sucrosewater and food-pellets
reinforcers, indicating that the pressing of the lever maintained by
food-pellet reinforcers was similarly resistant to the suppressive
effects of haloperidol to the pressing of the lever maintained by
sucrose-water reinforcers. Thus, only for Group F-W the cumulative
proportional rate-suppressive effects of haloperidol, summarized using
the [bar.p] statistic, were greater for lever presses maintained by
food-pellets than for lever presses maintained by sucrose-water
reinforcers. Again, this finding does not appear to be consistent with
the anhedonia hypothesis; why should pressing the lever maintained by a
reinforcer with high hedonic value be less resistant to the disruptive
effects of haloperidol?

Conclusions

[FIGURE 6 OMITTED]

In summary, under VI schedules, presentation of 45 mg food pellets
maintained more responding than did 0.05 cc of 5% sucrose, suggesting
that the pellets were more effective reinforcers. However, responding
maintained by the sucrose solution was slightly more resistant to
disruption by haloperidol (at least as quantified by p). In our view, an
interpretation based upon "anhedonia" produced by dopamine
blockade would be an oversimplification and would be potentially
misleading.